Paclitaxel, a naturally occurring diterpenoid extracted from yew trees, has demonstrated great potential as an anti-cancer drug. It is unique among antimitotic drugs in that it promotes the assembly of stable microtubules from tubulin. It binds strongly to microtubules, thus preventing depolymerisation of the tubulin and inhibiting mitosis. The structure of paclitaxel and the numbering system conventionally used is shown below. This numbering system is also applicable to compounds used in the process of the present invention.

The acyclic portion attached to the 13-hydroxy group is commonly referred to as “side chain” of a taxane compound.
Docetaxel, a paclitaxel derivative, has also demonstrated excellent antitumor activity over the past few years. Docetaxel has the following structure:

The chemical conversion of naturally occurring precursors such as 10-deacetylbaccatin III to paclitaxel and docetaxel have been reported. However, another potential precursor, 9-dihydro-13-acetylbaccatin III (9-DHAB-III), is abundant in needles and stems of the Canada yew, Taxus canadensis. The taxane structure of naturally occurring 9-DHAB-III has the carbon skeleton of paclitaxel and docetaxel except for the lack of a side chain and an alpha-hydroxyl group at C9. 9-DHAB-III has the following structure:

Synthetic routes that have been proposed for the synthesis of biologically active taxanes from 9-DHAB-III involve its conversion to baccatin III, 10-deacetylbaccatin III and 7-protected derivatives thereof. In this approach, a 7-protected-9-DHAB-III is oxidised at C9 followed by deacetylation at C10 and/or C13 (U.S. Pat. No. 6,197,981). Others have used 9-DHAB-III as starting material to produce novel 9-dihydro taxanes with potentially greater therapeutic benefits.
Important limitations and difficulties associated with existing methods using 9-DHAB-III as starting material include the difficult and low yield of deacetylation at 13-hydroxy group, poor scalability and the limited versatility of synthetic intermediates.
Earlier methods for the transformation of 9-DHAB III to 9-ketotaxanes bearing side chains involved the oxidation of the 9-hydroxy group prior to connecting the side chain to the baccatin A ring. A major difficulty with this approach is that the 13-acetoxy group of 7-protected-9-keto-baccatin III resists hydrolysis. Its removal requires strong bases such as alkyl lithium and the prior hydrolysis of the 10-acetoxy group resulting in overall low yield.
Another disadvantage is that the protection of the 7-hydroxy and 10-hydroxy groups in the synthesis of docetaxel and analogs thereof requires a separate step for protection of each position.
Therefore, additional routes for the production of biologically active taxanes are still needed.
It would thus be highly desirable to be provided with a new process for the preparation of paclitaxel, docetaxel, 9-dihydrobaccatin III, baccatin III and other taxanes from 9-DHAB-III.